Refinement of the locus for distal hereditary motor neuronopathy VII (dHMN-VII) and exclusion of candidate genes.
Distal hereditary motor neuronopathy type seven (dHMN-VII) is an autosomal dominant condition characterized by distal muscular atrophy associated with unilateral or bilateral vocal cord paralysis. We previously mapped the dHMN-VII locus to chromosome 2q14 using a genome-wide linkage scan in a single large pedigree. Here we have performed more detailed microsatellite saturation analysis and also evaluated two new affected individuals not described in the original study. We have significantly refined the extent of the disease locus and show that two distinct regions of chromosome 2q14.2, comprising 9.2 Mb and 4.3 Mb separated by an unusual double recombination event, cosegregate with the disease phenotype. The proximal linked region is now defined by markers D2S3038-D2S160, and the distal region by D2S2970-D2S2969. Sequencing of 15 candidate genes within the critical interval has not yet revealed any pathogenic mutations. Inspection of genomic databases indicates that this refinement of the critical interval by 8.4 Mb reduces the number of candidate genes from approximately 400 to approximately 100.
Dick
Katherine J
KJ
Department of Medical Genetics, St George's University of London, Cranmer Terrace, London SW17ORE, United Kingdom.
McEntagart
Meriel
M
Alwan
Wisam
W
Reilly
Mary
M
Crosby
Andrew H
AH
D000328:Adult; D001483:Base Sequence; D002874:Chromosome Mapping; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005799:Genes, Dominant; D015417:Hereditary Sensory and Motor Neuropathy / Q000235:genetics*; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
D017931:DNA Primers